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Cartilage Protection: Evidence from In Vivo Studies

Three main therapeutic pathways have been described for the treatment of osteoarthritis:

therapies that relieve symptoms
therapies that increase the production of cartilage matrix components
therapies that inhibit cartilage destruction 1.

ASU ExpanscienceTM may play a role in osteoarthritis by helping cartilage to regenerate and by preventing its erosion. Indeed, Avocado Soybean Unsaponifiables are thought to help cartilage repair by causing cartilage cells to produce extra TGF-ß. Avocado Soybean Unsaponifiables are also able to inhibit inflammatory mediators as well as molecules known to destroy the cartilage matrix (e.g. MMP-3) 2.
Several in vivo studies (i.e. studies conducted in animals) have confirmed in vitro data showing that a regulatory effect of ASU ExpanscienceTM on specific molecular targets might protect cartilage. Data gathered from in vitro and in vivo studies are important since they help shed light on the potential mechanistic role of ASU ExpanscienceTM in osteoarthritis.


In vivo studies show:

ASU ExpanscienceTM increase tissue-regenerating promoting mediators 3

In a study where dogs received ASU daily or every three days, increased levels of TGF-ß1 and TGF-ß2 were found in knee joint fluid as previously suggested in vitro. This study also demonstrated that high levels of TGF-ß are associated with the production of matrix components, such as collagen and proteoglycans, by cartilage cells (see figure).

ASU Expanscience TM treatment is associated with increased TGF-ß levels in canine knee joint fluid (Adapted from Altinel et al.3

ASU Expanscience TM treatment is associated with increased TGF-ß levels in canine knee joint fluid (Adapted from Altinel et al.) 

ASU ExpanscienceTM show a positive effect on cartilage in various models 4

A study where rats with cartilage destruction were treated with ASU ExpanscienceTM orally daily for 2 weeks, reduced loss of glycosaminoglycan (found in cartilage and synovial fluid) and hydroxyproline (a major component of collagen) content in the granuloma tissue was observed. In addition, the proliferation of hydroxyproline and ß-D-glucosaminidase activity of the granuloma tissue was found to be significantly reduced. These data show preservation of the implanted cartilage thus suggesting that ASU ExpanscienceTM might exert a chondroprotective effect possibly through an anti-inflammatory action (see figure).

ASU Expanscience TM decreases the loss of cartilage matrix components in rats (Adaptated from Khayyal et al. 4

ASU Expanscience TM decreases the loss of cartilage matrix components in rats (Adaptated from Khayyal et al.) 

A study where osteoarthritis was modeled / simulated in sheeps had simulated osteoarthritis provided further evidence for a role for ASU ExpanscienceTM as a disease-modifying agent. ASU ExpanscienceTM treatment provided a significant positive effect on cartilage as measured by higher proteoglycan content and thicker knee-joint cartilage. A reduction in bone sclerosis (hardening of the bones associated with osteoporosis) was also seen with ASU ExpanscienceTM. The data suggest an additional 'anabolic effect' on cartilage cells, which lead to the production of matrix components (see figure) 5.

Potential functions of ASU Expanscience TM on cartilage homeostasis 

Potential functions of ASU Expanscience TM on cartilage homeostasis 

 

1. Henrotin YE, Labasse AH, Jaspar JM, De Groote DD, Zheng SX, Guillou GB et al. Effects of three avocado/soybean unsaponifiable mixtures on metalloproteinases, cytokines and prostaglandin E2 by human articular chondrocytes. Clin Rheumatol 1998; 17 : 31-39.
2. Reginster JY, Bruyere O, Henrotin Y. New perspectives in the management of osteoarthritis. Structure modification: facts or fantasy? J Rheumatol (Suppl) 2003; 67: 14 20.
3. Altinel L, Saritas ZK, Kose KC, Pamuk K, Aksoy Y, Serteser M. Treatment with unsaponifiable extracts of avocado and soybean increases TGF beta1 and TGF beta2 levels in canine joint fluid. Tohoku J Exp Med 2007;211:181 6.
4. Khayyal MT, el Ghazaly MA. The possible 'chondroprotective' effect of the unsaponifiable constituents of avocado and soya in vivo. Drugs Exp Clin Res 1998; 24: 41 50.
5. Cake MA, Read RA, Guillou B, Ghosh P. Modification of articular cartilage and subchondral bone pathology in an ovine meniscectomy model of osteoarthritis by avocado and soya unsaponifiables (ASU). Osteoarthritis Cartilage 2000; 8: 404 11.